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Abstract：
BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications.
METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility.
RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71).
CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.
METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility.
RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71).
CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.
摘要：
背景：传统上对疑似遗传性癌症综合征的患者进行生殖系基因检测，以加强癌症监测和/或预防策略，但越来越多地用于治疗适应症。
方法：我们对在我们中心接受种系基因检测的患者进行了回顾性研究，以确定可操作致病性种系变异（PGV）的患病率及其临床应用。
结果：从2000年到2022年，1154名癌症患者接受了种系测试，大多数（945/1154）使用多基因面板进行了测试。41111名（35.6％）患者患有PGV，334名（81％）具有临床可行性。BRCA1/2占可操作突变的62.3%，其次是错配修复(18%)，和其他同源重组修复(HRR)基因(19.7%)。一百五十二名种系阳性患者患有晚期癌症，79例接受了种系定向治疗(聚ADP核糖聚合酶抑制剂=75;免疫疗法=4).免疫治疗和多聚ADP核糖聚合酶的中位持续时间为20.5个月（范围5-40个月）和8个月（范围1-76个月），分别。在接受铂类化疗的BRCA/HRR突变携带者中，新辅助治疗组的病理完全缓解率为53%(n=17例乳腺癌),晚期治疗组的客观缓解率>80%(n=71).
结论：接受测试的癌症患者中有三分之一携带PGV，约80％具有临床可行性。在现实世界中，四分之三的种系阳性晚期癌症患者接受了种系指导的治疗，强调种系测试在指导癌症治疗方面的实用性。
方法：我们对在我们中心接受种系基因检测的患者进行了回顾性研究，以确定可操作致病性种系变异（PGV）的患病率及其临床应用。
结果：从2000年到2022年，1154名癌症患者接受了种系测试，大多数（945/1154）使用多基因面板进行了测试。41111名（35.6％）患者患有PGV，334名（81％）具有临床可行性。BRCA1/2占可操作突变的62.3%，其次是错配修复(18%)，和其他同源重组修复(HRR)基因(19.7%)。一百五十二名种系阳性患者患有晚期癌症，79例接受了种系定向治疗(聚ADP核糖聚合酶抑制剂=75;免疫疗法=4).免疫治疗和多聚ADP核糖聚合酶的中位持续时间为20.5个月（范围5-40个月）和8个月（范围1-76个月），分别。在接受铂类化疗的BRCA/HRR突变携带者中，新辅助治疗组的病理完全缓解率为53%(n=17例乳腺癌),晚期治疗组的客观缓解率>80%(n=71).
结论：接受测试的癌症患者中有三分之一携带PGV，约80％具有临床可行性。在现实世界中，四分之三的种系阳性晚期癌症患者接受了种系指导的治疗，强调种系测试在指导癌症治疗方面的实用性。
